Hepatitis B virus (HBV) is a member of the Hepadnavirus family, and causes acute and chronic hepatitis. About 350 million people of the world's population, in particular, 5˜8% of the people in Korea and China, are chronic HBV patients, and HBV is a main cause of liver diseases and liver cancer. Although the development of a vaccine against HBV has made it possible to prevent hepatitis B, but still many people are suffering from chronic hepatitis by HBV infection. The HBV infection induces hepatitis and liver cirrhosis as well as liver cancer, and the incidence of liver cancer in chronic hepatitis patients is 300 fold higher than the normal. The WHO (World Health Organization) revealed that about 80% of liver cancers result from chronic hepatitis B by HBV infection.
Currently available therapeutic drugs for hepatitis B include nucleoside analogues, such as lamivudine, adefovir dipivoxil, and others, and they are known to inhibit HBV DNA polymerase. However, resistant viruses emerge in 75% of the patients after three-years of administration therewith, leading to decreased therapeutic efficacies, and thus, they are used in combination with hepatitis B antibody agents so as to prevent vertical transmission or infection after liver transplantation.
The hepatitis B antibody agents currently used are prepared from human blood sources having anti-HBV antibodies using highly technical purification and virus inactivation methods, but such methods cannot meet the ever-rising demand due to the low availability of expensive human plasma with high anti-HBV antibody as well as the high cost of inactivating the plausible human plasma-derived viruses.
Ever since a methodology of preparing a monoclonal antibody (mAb) was established by Köhler and Milstein (1975), monoclonal antibodies derived from mice have been mainly used for diagnosis or some treatment. However, the mouse antibody cannot be administered due to possible generation of human anti-mouse antibody (HAMA) when applied to a human body for therapeutic purpose. In order to solve the problems of HAMA, there have been developed chimeric and humanized antibodies. The chimeric antibody contains the variable regions (Fv fragment) of mouse mAb which constitutes ˜30% of whole antibody molecule. In contrast, the humanized antibody contains the CDRs (complementarity determining regions) of mouse mAb which constitutes ˜10% of whole antibody molecule. Although such chimeric and humanized antibodies reduced the HAMA reaction significantly, it might be better to use human antibodies in the treatment of chronic disease such as chronic hepatitis which requires a long-term and continuous administration.
The present invention has endeavored to develop novel, improved antibodies and found that such antibodies can be used to inactivate HBV by binding to the HBV-surface antigen.